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Ovulation packet Implantation and Placenta Gwen V. Childs, Ph.D. Freshly Ovulated oocyte This oocyte is seen in the center of a mass of cumulus cells. Secondary oocyte is arrested in metaphase of meiosis II. During the ovary lecture, we left the oocyte right after ovulation and focused on the events that set up the uterine endometrium for implantation. In the meantime, the oocyte + cumulus + corona radiata has been picked up by the fimbriated end of the oviduct. It is transported to the ampulla where it will be fertilized. Fertilization and transport Fertilization occurs in ampulla of oviduct The oocyte completes meiosis and the pronucleus joins with the sperm pronucleus, restoring the diploid state. The zygote is then transported to the uterine lumen. The embryo develops to the morula and blastocyst stages and implants as a blastocyst. 1 Implantation Lacunar spaces Trophoblast cells begin to invade uterine endometrium. Digs deeper and eventually is enclosed in the endometrium. Uterine endometrium is in secretory stage, build up of glands and stroma that contain glycogen and other nutrients for embryo. Trophoblast over the inner cell mass differentiates into cytotrophoblast and syncytiotrophoblast. Cytotrophoblast layer divides and adds cells to the syncytium in the syncytiotrophoblast layer Syncytiotrophoblast by days 12-13 develop lacunae, spaces. As they invade, they break down maternal vessels (sinusoids) and the maternal blood spills in these spaces. Invasion continues and this becomes the initial route for the maternal blood support. Third week Projections of syncytiotrophoblast. Also include columns of cytotrophoblast. Don’t have any extraembryonic mesenchyme yet. Primary villi (end of second week) Mesenchyme grows into primary villus and this forms a secondary villus. Mesenchyme will serve as a substrate and support for outgrowth of blood vessels. Once blood vessels have grown out, the villus is a tertiary villus. 2 Placental Blood supply Tertiary villi Anchoring villus Stem villus Young placenta: Tertiary villus Free villus Older placenta Cytotrophoblast is gone leaving only the syncytiotrophoblast Need Tertiary, free villi Young placenta for closer connection between vessels (maternal and fetal) 3 Older placenta The placenta as an endocrine organ The syncytiotrophoblast produces human chorionic gonadotropin (identical to LH) which rescues and maintains the corpus luteum for about 60 days. As it develops, it also produces other types of hormones: thyrotropin, somatomammotropin, estrogens and progesterone. Eventually maintains uterine lining. Syncytiotrophoblast requires androgens to make estrogens: Gets them from fetal adrenal Anchoring villi How does the uterus respond? As the blastocyst penetrates the endometrium, it repairs the penetration defect with a fibrin coagulum. Endometrial stroma become edematous and vascular. Glands secrete glycogen and mucus. 4 What stroma looked like before implantation Response of Uterus Secretory stage: Stroma cells small; Spaces with edema Stroma becomes a “decidua”; Cells enlarge and become foamy. Response of uterus Regional specialization of uterus Decidua basalis Decidua capsularis Syncytiotrophoblast invading uterine endometrium. Decidua parietalis Decidual cell 5 Theory about what prevents an immune reaction against the placenta Father’s genes produce antigens, yet placenta is immunoprotected. The placenta does not express class II histocompatibility antigens. The class I histocompatibility antigens that it does express (HLA-E and HLA-G) are only weakly immunogenic. The cells of the placenta secrete progesterone, which is immunosuppressive. More theories: Placenta foils the T cells In rats, the embryos (and the mother's endometrium) secrete corticotropinreleasing hormone (CRH). Induces the expression of Fas ligand (FasL) on the cells of the placenta. Activated T cells express Fas so any threatening T cells would commit suicide by apoptosis when they encounter FasL In mice, the cells of the placenta degrade the amino acid tryptophan. Tryptophan is essential for T-cell function. (D. H. Munn, et. al., Science, 281: 1191, 21 Aug 1998.) What about the placenta in twin pregnancies? Monozygotic twins Example from dizygotic twins 6 IVF Retrieval Oocyte retrieval (see needle) Graafian follicles after stimulation; retrieved about 12 eggs from both ovaries. Development after in vitro fertilization 8 cell embryo and assisted hatching and co-culture Polar body Pronuclei of fertilized ovum 7 Human blastocysts Embryo transfer: yellow dots indicate transfer Tube. Green=uterine lumen; blue=uterus For women who are 35-39, they recommend transfer of 4-5 embryos (So, Couple can freeze the rest). With a 55% success rate, they are likely to have twins. 8